DEMENTIA 2017 Unforgettable, that s what you are... Recorded by Nat King Cole, 1951, lyrics by Irving Gordon William T. Wake, M.D., F.A.A.F.P. Kaiser Permanente Departments of Family Medicine and Geriatrics, Palliative Medicine & Continuing Care A mind is a terrible thing to waste. -Official motto of the United Negro College Fund A wrong-doer is often a man that has left something undone, not always he that has done something. Marcus Aurelius Antoninus A.D. 121-180 Disclosures 1997 2002 Lecturer on Pfizer Speaker s Bureau Stockholder, Pfizer Generic names will be used No recommendation of company products 1
Dementia Is Personal The challenge we face We are seeing an aging population among our patients Elderly individuals are living longer than before The prevalence of dementia increases with age Larger numbers of our patients will present to our offices with dementia Many of our current patients are being underserved, undermanaged, undertreated and ignored Money and resources are being squandered Patients and their families are looking to us for help We need to be providing care for these patients as well History of Dementia Senility Auguste Deter Dr. Alois Alzheimer 2
Auguste Deter s Autopsy Brain was significant for numerous abnormal findings: Amyloid plaques Neurofibrillary tangles Findings presented at a conference November 3 1906 Pathologic features of Alzheimer s disease Presenile Dementia Alzheimer s disease considered to be a disorder of younger patients Mimic natural progression of senility Retrospective analysis of senile elderly revealed the same pathognomonic features Senility is and always has been dementia Dementia Diminished mental function is not a natural consequence of the aging process Dementia is always pathologic Individuals with dementia need to undergo a complete and thorough medical evaluation 3
Prevalence of Dementia Demographics Women are at greater risk for developing dementia than men May be due to longer lifespan African Americans twice as likely as whites to develop dementia Hispanic Americans are 1.5 times more likely than non-hispanic whites from Nowrangi MA, Rao V & Lyektsos CG. Epidemiology, Assessment, and Treatment of Dementia. Psychiatric Clinics of North America.2011;(34, Issue 2): 275 294 Differential Diagnosis of Dementia Diagnosis % Diagnosis % Alzheimer s disease 56.8 Huntington s disease 0.9 Vascular 13.3 Mixed 0.8 Depression 4.5 Infection 0.6 Alcohol 4.2 Subdural hematoma 0.4 Normal Pressure Hydrocephalus 1.6 Traumatic Brain Injury Metabolic 1.5 Anoxic 0.2 Drugs 1.5 Miscellaneous 3.7 Parkinson s disease 1.2 13.2% of diagnoses are potentially reversible 0.4 4
Mild Cognitive Impairment (MCI) Patient is cognitively impaired, but is not demented Clinical criteria: Cognitive complaint Cognitive impairment (usually memory) Essentially normal cognition Preserved activities of daily living Not demented Prevalence of MCI From Graham JE, et al. Prevalence and severity of cognitive impairment with and without dementia in an elderly population. Lancet 1997; 349:1793-96 MCI & Dementia Patients with MCI will progress to Alzheimer s disease at a rate of 10% to 15% per year Healthy control subjects convert at a rate of 1% to 2% per year From Petersen RC, et al. Current Concepts in Mild Cognitive Impairment.Arch Neurol 2001;58:1985-1992 5
Dementia & Co-morbidity Other medical disorders can contribute to the demented state Other conditions can be identified during the dementia evaluation Costs of Dementia Higher hospitalization rates Higher emergency room utilization Decreased adherence with therapy for other medical conditions Increased utilization of extended care facilities Medical Cost Savings With Improvement of Cognitive Status Savings If MMSE Score Is Raised Savings If MMSE Score Is Prevented From Falling Original MMSE score From Ernst RL, Hay JW, Fenn C, TinklenbergJ & Yesavage JA. Cognitive function and the costs of Alzheimer disease. Arch Neurol 1997;54:687-693 6
Advance Planning Involve patients in earlier stages of disease Legal & economic decisions Identify responsible parties Estate planning POLST Living Arrangements Who does patient live with? Who is available? Consider referral to Care Guidance (on ereferral) Driving Patients with mild dementia at no greater risk of causing accidents Anyone with moderateto-severe dementia at greater risk of causing accidents MMSE < 20 Mid-range and lower scores on other assessment scales 7
Who Has Dementia? Missed appointments Prescriptions unfilled Concern of family Worsening of other medical conditions Rising HgbA 1 c Elevated blood pressure Deteriorating lipid control Unexplained weight loss Development of pressure ulcers Increased rates of ER/UC visits & hospital admissions Assessment of memory Occasional lapses of memory are normal Context is important Consider functional status Utilize objective measure Memory tests There are many published quick memory tests for primary care practice Few have established reliability or predictive value Folstein Mini-Mental State Examination (MMSE) is the most famous Helpful in designating stages Capacity determination Driving 8
Problems With MMSE Lack of sensitivity Language availability Spanish version available Limited other languages Proprietary Copyrighted Legal experts doubt that copyright holders can claim exclusivity Alternatives to MMSE SLUMS (St. Louis University Mental Status) Used by VAMC www.stlouis.va.gov/grecc/slums_details.pdf MOCA (Montreal Cognitive Assessment) Consortium of specialists in dementia, including UCLA Multiple languages www.mocatest.org Sensitivity of MOCA From Nasreddine ZS, Phillips NA, Bédirian V, Charbonneau S, Whitehead V, Collin I, Cummings JL & Chertkow H. The Montreal Cognitive Assessment, MoCA: A Brief Screening Tool For Mild Cognitive Impairment. J Am Geriatr Soc 2005;53:695-699 9
Assessment of mood Depression is a cause of decreased mental function in the elderly Depression can also be incipient symptom of Alzheimer s disease Geriatric Depression Scale Scoring: Normal 0-5, above 5 may suggest depression Workup Laboratory: Strongly recommended: CBC, Electrolytes, Calcium, Glucose, Creatinine, Albumin, TSH, B 12 level, Serologic test for syphilis Consider for special circumstances: HIV, ESR, ANA, Heavy metal screen, Drug screens Neuroimaging Looking for tumors, subdural hematomas, normal pressure hydrocephalus 3.5% of patients with dementia CAT scan perfectly adequate 10
Neuroimaging Generalized cerebral atrophy is nonspecific and is normal with age Look for periventricular atrophy Diagnosis of Alzheimer s Disease Progressive cognitive decline Normal mood Lack of other causative medical condition Lack of structural abnormality in the brain Pillars of Treatment Treating the disease Treating the symptoms Supporting the patient Supporting the caregiver 11
Treatment Options Cholinesterase inhibitors Monotherapy only for mild dementia N-methyl-D-aspartate (NMDA) receptor antagonists Can be used in monotherapy Best when combined with cholinesterase inhibitors for moderate-to-severe dementia In patients with severe dementia, treatment with NMDA receptor antagonists & cholinesterase inhibitors may help to decrease psychotic episodes Histochemical actions of cholinesterase inhibitors Affected neurons noted to have cholinergic synapses on dendrites Cholinergic-depleted brains demonstrate memory deficit Cholinesterase inhibitors may enhance trophic effects on non-affected neurons Comparisons Dosing Rivastigmine (Exelon) BID (SR available) Galantamine (Razadyne) BID (SR available) Donepezil (Aricept) QD Tolerability ++ +++ ++++ Possible dosage adjustment Dosage forms Generic availability - Renal/liver disease - Pill, liquid & Pill & liquid Pill patch Yes Yes Yes No required testing for any of these agents 12
Considerations All cholinesterase inhibitors are effective No good comparison trials have been published None will probably ever be conducted Start with lowest dose, and increase dosage stepwise, over 4-6 weeks Improvement in mental function will occur over one year Considerations (continued) Stopping medication will result in loss of acquired function If medication is restarted shortly after cessation, lost function may be re-attained Increasing dosage above recommended dose may be counterproductive Some anecdotal evidence for improvement of function when patients are switched from one agent to another Actions of glutamate Damage to neurons is associated with enhancement of excitatory neurotransmitters, especially glutamate. Activation of glutaminergic receptors, especially the N-methyl-D-aspartate (NMDA) receptor channel complex, leads to a pronounced increase in toxic intracellular calcium ion. 13
Actions of glutamate (continued) The hippocampus and the middle layers of cerebral cortex are regions high in glutamate receptors. Memantine Moderate-affinity, uncompetitive, NMDA receptor antagonist Combination of memantine and donepezil given to patients with moderate-to-severe Alzheimer's disease for 24 weeks Patients treated with combination showed significant improvement in all measures of cognitive function when compared to donepezil/placebo treated patients Can be used with any cholinesterase inhibitor Future Prospects Immunotherapy Inhibitors of -amyloid production Nerve growth factor (NGF) 14
Complications of Dementia Depression Psychosis/Delusions Wandering Sleep disturbances Antidepressant Use in Dementia Medication Clomipramine Moclobemide (MAOI, not available in U.S.) Sertraline Citalopram Imipramine Fluoxetine Paroxetine Effect compared to placebo Superior Superior Superior Superior No difference No difference No difference Theoretically, venlafaxine, mirtazapine, secondary amine TCAs, or a MAOI may be effective, but little to no research has been done From Lyketsos CG, Olin JT. Depression in Alzheimer's disease: overview and treatment. Biol Psychiatry. 2002;52243-252 Delusions/Psychosis Most conventional antipsychotic medications will worsen cognitive function in patients with Alzheimer's disease Treat behaviors that place the patient at risk for harm to himself or to others Intervene only if the behavior impairs functional capacity or interferes with the delivery of needed medical care 15
Atypical antipsychotics Long-term treatment with antipsychotics Recent reports of increased health risks with long-term use of antipsychotics May be selection bias Until prospective, double-blind placebocontrolled studies are completed, we should limit treatment to as little a time as possible Valproic acid Several studies have shown that valproic acid is useful for treatment of psychosis associated with dementia Few ill effects reported Routine monitoring of CBC s, liver functions and therapeutic drug levels are recommended Monitoring drug levels to help prevent overtreatment 16
Use ID bracelets, necklaces Install exit alarms Wandering Sleep disturbances Decline of both REM and non-rem sleep with progression of Alzheimer's disease Non-pharmacologic treatment is preferable: Reduce daytime naps Restrict time in bed Increase daytime activity Exposure to bright light, especially sunlight, during waking hours If medication used, one should use short-acting agents Trazodone is particularly helpful Hospice Hospice & Palliative Care Criteria very restrictive Ability to speak six or less words Cannot walk without personal assistance Cannot sit up without assistance Loss of ability to smile Loss of ability to hold up head independently MMSE 0/30 17
Hospice & Palliative Care (continued) Hospice (continued) Patients should have had one of the following within the past 12 months: Aspiration pneumonia Multiple stage 3 and 4 pressure ulcers Pyelonephritis Septicemia Recurrent fever after antibiotics Inability to maintain sufficient fluid and calorie intake 10% weight loss during the previous six months Serum albumin <2.5 gm/dl Hospice & Palliative Care (continued) Palliative care Homebound or taxing effort to leave home Skilled need: Wound(s) Catheter Feeding tube Managed symptom(s): Pain Behavioral issues Constipation Hospice & Palliative Care (continued) Many patients with dementia will qualify for Hospice or Palliative Care due to concurrent conditions 18
Prevention Currently no effective preventive treatment To develop Alzheimer s disease requires damage and dysfunctional repair Dysfunctional repair is inherited, damage is acquired Viruses Radiation Toxins Trauma Alcohol Damage Infarcts Dysfunctional repair Alzheimer s Disease Caring For the Caregivers Depression 30-55% of caregivers Independent of the severity of family members dementia Elevated blood pressure & lipids Lack of exercise & sleep Increased use of psychoactive substances Health effects of caregiving persist for over 4 years after the death of the demented family member or placement in a long-term nursing facility 19
HealthConnect tools SmartSets for Dementia are available Dementia SmartPhrases, MMSE, Geriatric Depression Scale and a treatment instruction message are available in the Geriatric Folder at http://dms.kp.org/docushare/dsweb/view/collection- 53545 Conclusion Evaluate Treat Advocate 20